Induction of distinct phenotypes in clonal and variant GH4 pituitary cells

GH cells are a widely used cell strain for the investigation of mechanisms regulating hormone release and synthesis. This report identifies two inducible phenotypes of the GH4 clone (epithelioid and motile) which may extend studies of this well-characterized cell line to different stages of pituitary cell development. GH4C1 cells treated in suspension with epidermal growth factor plus tetradecanoylphorbol acetate aggregate to form large epithelioid colonies with extensive cell-to-cell and cell-to-substratum adhesion. These cells cease replicating within 48 h, increase 50% in cell volume, and synthesize 40-fold more prolactin. A GH4C1 variant with enhanced substratum adhesion and little or no cell-to-cell adhesion (GH4S1), responds differently to this treatment. These cells cease replicating immediately, show increased cell separation, develop leading lamellae, and display locomotory activity. Each phenotype coexists in mixed cultures of GH4C1 and GH4S1 cells. This indicates that the different inducible response of the variant does not result from autocrine secretion. A molecular basis for cell-to-cell adhesion in GH4 cells was investigated. GH4C1, but not the variant cells, express a 180 kDa immunoreactive protein indistinguishable from an isoform of the neural cell adhesion molecule. Therefore the absence of cell-to-cell adhesion and inability to develop extensive cell-to-cell adhesion characteristic of the epithelioid phenotype may result from altered expression of the neural cell adhesion molecule. These findings are important because they have defined an in vitro approach to investigate genetic and cellular changes associated with the development and progression of pituitary cell phenotype.